MCID: 3MT016
MIFTS: 40

3-Methylglutaconic Aciduria, Type Iii

Categories: Genetic diseases, Eye diseases, Metabolic diseases, Rare diseases, Cardiovascular diseases

Aliases & Classifications for 3-Methylglutaconic Aciduria, Type Iii

MalaCards integrated aliases for 3-Methylglutaconic Aciduria, Type Iii:

Name: 3-Methylglutaconic Aciduria, Type Iii 54 39 13
3-Methylglutaconic Aciduria Type 3 12 23 24 25 56 29 14 69
Costeff Optic Atrophy Syndrome 12 23 24 25 56 71
Costeff Syndrome 12 23 24 25 56 71
Optic Atrophy Plus Syndrome 23 24 25 71
Mga3 12 25 56 71
Infantile Optic Atrophy with Chorea and Spastic Paraplegia 12 25 56
3-Methylglutaconic Aciduria Type Iii 12 24 25
Autosomal Recessive Optic Atrophy Plus Syndrome 12 56
Opa3-Related 3-Methylglutaconic Aciduria 39 23
Autosomal Recessive Optic Atrophy Type 3 12 56
3-Alpha-Methylglutaconic Aciduria Type 3 71
Autosomal Recessive Optic Atrophy 3 25
Optic Atrophy 3 Autosomal Recessive 71
Iraqi-Jewish Optic Atrophy Plus 12
Iraqi Jewish Optic Atrophy Plus 25
3-Methylglutaconic Aciduria 3 71
Optic Atrophies, Hereditary 42
Autosomal Recessive Opa3 25
Mga, Type Iii 25
Mga Type Iii 71
Opa3 Defect 25
Mgca3 71

Characteristics:

Orphanet epidemiological data:

56
3-methylglutaconic aciduria type 3
Inheritance: Autosomal recessive; Age of onset: Childhood;

OMIM:

54
Inheritance:
autosomal recessive

Miscellaneous:
onset of optic atrophy in infancy or early childhood
neurologic features occur later in childhood
increased prevalence in individuals of jewish-iraqi origin
allelic disorder to autosomal dominant optic atrophy and cataract


HPO:

32
3-methylglutaconic aciduria, type iii:
Inheritance autosomal recessive inheritance


Classifications:



Summaries for 3-Methylglutaconic Aciduria, Type Iii

Genetics Home Reference : 25 Costeff syndrome is a condition characterized by vision loss, movement problems, and intellectual disability. People with Costeff syndrome have degeneration (atrophy) of the optic nerves, which carry information from the eyes to the brain. This optic nerve atrophy often begins in infancy or early childhood and results in vision loss that worsens over time. Some affected individuals have rapid and involuntary eye movements (nystagmus) or eyes that do not look in the same direction (strabismus).

MalaCards based summary : 3-Methylglutaconic Aciduria, Type Iii, also known as 3-methylglutaconic aciduria type 3, is related to behr syndrome and optic atrophy plus syndrome, and has symptoms including visual impairment, nystagmus and dysarthria. An important gene associated with 3-Methylglutaconic Aciduria, Type Iii is OPA3 (OPA3, Outer Mitochondrial Membrane Lipid Metabolism Regulator), and among its related pathways/superpathways are Amino Acid metabolism and Mitochondrial protein import. Affiliated tissues include eye and brain.

UniProtKB/Swiss-Prot : 71 3-methylglutaconic aciduria 3: A metabolic disorder that causes a neuro-ophthalmologic syndrome consisting of early-onset bilateral optic atrophy, spasticity, extrapyramidal dysfunction and cognitive deficit. Urinary excretion of 3-methylglutaconic acid and 3-methylglutaric acid is increased. MGA3 can be distinguished from MGA1 by the absence of increase of 3- hydroxyisovaleric acid levels.

OMIM : 54
Type III 3-methylglutaconic aciduria is a neuroophthalmologic syndrome consisting of early-onset bilateral optic atrophy and later-onset spasticity, extrapyramidal dysfunction, and cognitive deficit. Urinary excretion of 3-methylglutaconic acid and of 3-methylglutaric acid is increased (Anikster et al., 2001). The phenotype is similar to Behr syndrome (210000) and may in some cases represent the same disorder (Sheffer et al., 1992; Lerman-Sagie, 1995). (258501)

Disease Ontology : 12 A 3-methylglutaconic aciduria that has material basis in mutation in the OPA3 gene.

GeneReviews: NBK1473

Related Diseases for 3-Methylglutaconic Aciduria, Type Iii

Graphical network of the top 20 diseases related to 3-Methylglutaconic Aciduria, Type Iii:



Diseases related to 3-Methylglutaconic Aciduria, Type Iii

Symptoms & Phenotypes for 3-Methylglutaconic Aciduria, Type Iii

Symptoms via clinical synopsis from OMIM:

54

Head And Neck- Eyes:
optic atrophy
decreased visual acuity

Laboratory- Abnormalities:
increased urinary 3-methylglutaconic acid

Neurologic- Central Nervous System:
dysarthria
ataxia
hyperreflexia
spasticity
extensor plantar responses
more

Clinical features from OMIM:

258501

Human phenotypes related to 3-Methylglutaconic Aciduria, Type Iii:

56 32 (show all 17)
id Description HPO Frequency Orphanet Frequency HPO Source Accession
1 visual impairment 56 32 hallmark (90%) Very frequent (99-80%) HP:0000505
2 nystagmus 56 32 frequent (33%) Frequent (79-30%) HP:0000639
3 dysarthria 56 32 frequent (33%) Frequent (79-30%) HP:0001260
4 ataxia 56 32 frequent (33%) Frequent (79-30%) HP:0001251
5 choreoathetosis 56 32 hallmark (90%) Very frequent (99-80%) HP:0001266
6 intellectual disability 56 32 frequent (33%) Frequent (79-30%) HP:0001249
7 spastic paraparesis 56 32 frequent (33%) Frequent (79-30%) HP:0002313
8 3-methylglutaconic aciduria 56 32 hallmark (90%) Very frequent (99-80%) HP:0003535
9 gait disturbance 56 32 occasional (7.5%) Occasional (29-5%) HP:0001288
10 optic atrophy 32 HP:0000648
11 chorea 32 HP:0002072
12 hyperreflexia 32 HP:0001347
13 spasticity 32 HP:0001257
14 cognitive impairment 32 HP:0100543
15 reduced visual acuity 32 HP:0007663
16 babinski sign 32 HP:0003487
17 abnormality of extrapyramidal motor function 32 HP:0002071

UMLS symptoms related to 3-Methylglutaconic Aciduria, Type Iii:


ataxia, muscle spasticity, abnormality of extrapyramidal motor function

Drugs & Therapeutics for 3-Methylglutaconic Aciduria, Type Iii

Search Clinical Trials , NIH Clinical Center for 3-Methylglutaconic Aciduria, Type Iii

Cochrane evidence based reviews: optic atrophies, hereditary

Genetic Tests for 3-Methylglutaconic Aciduria, Type Iii

Genetic tests related to 3-Methylglutaconic Aciduria, Type Iii:

id Genetic test Affiliating Genes
1 3-Methylglutaconic Aciduria Type 3 29 24 OPA3

Anatomical Context for 3-Methylglutaconic Aciduria, Type Iii

MalaCards organs/tissues related to 3-Methylglutaconic Aciduria, Type Iii:

39
Eye, Brain

Publications for 3-Methylglutaconic Aciduria, Type Iii

Articles related to 3-Methylglutaconic Aciduria, Type Iii:

id Title Authors Year
1
The neuropsychological profile of patients with 3-methylglutaconic aciduria type III, Costeff syndrome. ( 25657044 )
2015
2
OPA3, mutated in 3-methylglutaconic aciduria type III, encodes two transcripts targeted primarily to mitochondria. ( 20350831 )
2010
3
3-Methylglutaconic aciduria type III in a non-Iraqi-Jewish kindred: clinical and molecular findings. ( 12126933 )
2002

Variations for 3-Methylglutaconic Aciduria, Type Iii

ClinVar genetic disease variations for 3-Methylglutaconic Aciduria, Type Iii:

6
id Gene Variation Type Significance SNP ID Assembly Location
1 OPA3 NM_025136.3(OPA3): c.143-1G> C single nucleotide variant Pathogenic rs80356523 GRCh37 Chromosome 19, 46057170: 46057170
2 OPA3 NM_025136.3(OPA3): c.320_337del18 (p.Gln108_Glu113del) deletion Pathogenic rs80356526 GRCh37 Chromosome 19, 46056975: 46056992
3 OPA3 NM_025136.3(OPA3): c.415C> T (p.Gln139Ter) single nucleotide variant Pathogenic rs28937899 GRCh37 Chromosome 19, 46056897: 46056897
4 ISCA2 NM_194279.3(ISCA2): c.229G> A (p.Gly77Ser) single nucleotide variant Pathogenic/Likely pathogenic rs730882246 GRCh38 Chromosome 14, 74494329: 74494329
5 PMPCA NM_015160.2(PMPCA): c.1066G> A (p.Gly356Ser) single nucleotide variant Pathogenic rs768643552 GRCh37 Chromosome 9, 139313082: 139313082
6 PMPCA NM_015160.2(PMPCA): c.1129G> A (p.Ala377Thr) single nucleotide variant Pathogenic rs753611141 GRCh38 Chromosome 9, 136418847: 136418847
7 OPA3 NM_025136.3(OPA3): c.539A> G (p.Ter180Trp) single nucleotide variant Likely pathogenic rs1057516497 GRCh38 Chromosome 19, 45553515: 45553515

Expression for 3-Methylglutaconic Aciduria, Type Iii

Search GEO for disease gene expression data for 3-Methylglutaconic Aciduria, Type Iii.

Pathways for 3-Methylglutaconic Aciduria, Type Iii

Pathways related to 3-Methylglutaconic Aciduria, Type Iii according to GeneCards Suite gene sharing:

id Super pathways Score Top Affiliating Genes
1 10.91 AUH MDH1
2 10.59 DNAJC19 PMPCA TIMM8A

GO Terms for 3-Methylglutaconic Aciduria, Type Iii

Cellular components related to 3-Methylglutaconic Aciduria, Type Iii according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 mitochondrial inner membrane GO:0005743 9.35 C19orf70 DNAJC19 PMPCA TIMM8A TMEM70
2 mitochondrion GO:0005739 9.28 AUH C19orf70 DNAJC19 MDH1 OPA3 PMPCA

Sources for 3-Methylglutaconic Aciduria, Type Iii

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 MedGen
42 MeSH
43 MESH via Orphanet
44 MGI
46 NCI
47 NCIt
48 NDF-RT
51 NINDS
52 Novoseek
54 OMIM
55 OMIM via Orphanet
59 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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